Contents

Introduction to prostate cancer

Natural history and staging of prostate cancer

Prostate cancer has many uncertainties associated with its management. A major problem for any
review at present arises from the difficulty in establishing with certainty that the cancer is confined to
the prostate at the time of diagnosis.

Currently, through a combination of PSA measurement and ultra-sound-guided biopsy, it is now
possible to establish with greater certainty than before the local extent of the cancer within the gland
and its likely aggressiveness by application of the Gleason scoring system. This information, when
incorporated with other measurable factors into nomograms, has enabled clinicians to establish the
probability but not the certainty of the cancer being confined to the prostate.

Before the introduction of PSA it was easier to be certain that a person had metastatic disease on the
basis of a positive bone scan or computed tomography (CT). Unfortunately, while the bone scan has a
high level of specificity its sensitivity is too low and in current prostate cancer management, bone
scans have little use in determining the presence of metastatic disease. Consequently, after presumed
curative treatment for local disease, a rising PSA is now used as a surrogate marker for metastatic
disease. There is urgent need for a more sensitive and specific test to predict the metastatic potential
of an individual cancer.

This review initially intended to focus on metastatic disease, but for the reasons outlined above the
scope was expanded to include locally advanced as well as metastatic cancer. It is acknowledged that
it is often difficult to establish from published articles whether the disease was locally advanced or
metastatic because of the ‘grey zone’ resulting from the imprecision of our current staging modalities.
Locally-advanced disease for the purpose of the review has been defined as T3/T4 and/or early-stage
disease with PSA greater than 20.

Prostate cancer in Australia

The Australian Institute of Health and Welfare (2008) report[1] based on 2005 data predicted that the
risk of a male being diagnosed with cancer before age 75 was one in three and before age 85 was one
in two. Given that 29% of male cancers arise from the prostate, and assuming a relatively constant
pattern of the incidence of cancers as men age, prostate cancer is likely to continue to be a major male
health issue as our population ages. We know that approximately 3000 men die each year from
prostate cancer[2] and while earlier diagnosis and more aggressive local therapy have been available for
at least a decade, the death rate has not declined greatly. The age-standardised mortality rate in 1999
was 35 deaths per 100,000 males and in 2005 was 32.8 deaths per 100,000 males. It is also worthy of
note that 84% of deaths from prostate cancer in 2003 occurred in men over the age of seventy.

It is therefore evident that for the foreseeable future we will continue to need to care for a significant
number of older men with metastatic disease. A cure for metastatic cancer would be the ideal but
seems unlikely in the short term. The middle ground is to try to ensure the information currently
available is used appropriately to achieve optimal cancer control for these men while preserving the
best quality of life. The development of these guidelines is one step in trying to achieve this goal.

As part of the original plan no systematic review of evidence took place after (April) 2006. We
recognised that this is a limitation of the guidelines. We also recognised that there will need to be a
prolonged period of consultation as part of the process of acceptance of guidelines by the NHMRC
and this will add to the time between the end of the review and the final publication of the guidelines.
To try to in part to address this issue, we noted and provided references for high quality randomised
controlled trials where the review team believed that this more contemporary information may cause clinicians to reflect on the interpretation and relevance of the recommendations, given that the
recommendations were all based on the systematic review of the evidence available as of April 2006.
Another important consideration is the significant change in the way medicine is practised, with a
much greater focus on informed and shared decision making. The development of these guidelines has
provided the evidence base for the production of a consumer guide that will facilitate shared decision
making as men and their families confront the health issues associated with the management of
advanced and metastatic prostate cancer.